Pyranylphenyl hydroxyalkylnaphthoic acids are described in co-pending application, U.S. Ser. No. 834,912, filed Feb. 13, 1992, pending, which is a continuation-in-part of U.S. Ser. No. 662,535, filed Feb. 28, 1991, abandond, which are inhibitors of leukotriene biosynthesis. Said application is incorporated herein by reference and relevant portions thereof appear at the end of the Examples.
A key intermediate in the production of certain of said naphthoic acids is the lignan 7-hydroxy-3-hydroxymethyl-4-aryl-2-naphthoic acid, lactone form.
U.S. Ser. No. 662,535 teaches a multi-step, inherently low yield synthesis of this compound requiring several chromatographies.
Ward, Chem. Soc. Rev., 11, 75-125 (1982) and Pelter et al., J. Chem. Soc. Perkin Trans., 1603-1613 (1988), teach the synthesis of polyoxygenated lignans.
Pelter et al., J. Chem. Soc. Perkin Trans., 643-649 (1983) teach a synthesis for a mono-oxygenated lignan but Scheme 5 thereof indicates no regioselectivity in the ring closure step.